tbuckley/cabot-search huggingface dataset:
Mechanistic Insights of the LEMD2 p.L13R Mutation and Its Role in Cardiomyopathy
Authors: Ruping Chen, Simone Buchmann, Amos Kroth, Anahi-Paula Arias-Loza, Michael Kohlhaas, Nicole Wagner, Gianna Grüner, Alexander Nickel, Alexandra Cirnu, Tatjana Williams, Christoph Maack, Süleyman Ergün, Stefan Frantz, Brenda Gerull
Journal: Circulation Research (2023)

Nuclear envelope proteins play an important role in the pathogenesis of hereditary cardiomyopathies. Recently, a new form of arrhythmic cardiomyopathy caused by a homozygous mutation (p.L13R) in the inner nuclear membrane protein LEMD2 was discovered. The aim was to unravel the molecular mechanisms of mutant LEMD2 in the pathogenesis of cardiomyopathy.We generated a Lemd2 p.L13R knock-in mouse model and a corresponding cell model via CRISPR/Cas9 technology and investigated the cardiac phenotype as well as cellular and subcellular mechanisms of nuclear membrane rupture and repair.Knock-in mice developed a cardiomyopathy with predominantly endocardial fibrosis, left ventricular dilatation, and systolic dysfunction. Electrocardiograms displayed pronounced ventricular arrhythmias and conduction disease. A key finding of knock-in cardiomyocytes on ultrastructural level was a significant increase in nuclear membrane invaginations and decreased nuclear circularity. Furthermore, increased DNA damage and premature senescence were detected as the underlying cause of fibrotic and inflammatory remodeling. As the p.L13R mutation is located in the Lap2/Emerin/Man1 (LEM)-domain, we observed a disrupted interaction between mutant LEMD2 and BAF (barrier-to-autointegration factor), which is required to initiate the nuclear envelope rupture repair process. To mimic increased mechanical stress with subsequent nuclear envelope ruptures, we investigated mutant HeLa-cells upon electrical stimulation and increased stiffness. Here, we demonstrated impaired nuclear envelope rupture repair capacity, subsequent cytoplasmic leakage of the DNA repair factor KU80 along with increased DNA damage, and recruitment of the cGAS (cyclic GMP-AMP synthase) to the nuclear membrane and micronuclei.We show for the first time that the Lemd2 p.L13R mutation in mice recapitulates human dilated cardiomyopathy with fibrosis and severe ventricular arrhythmias. Impaired nuclear envelope rupture repair capacity resulted in increased DNA damage and activation of the cGAS/STING/IFN pathway, promoting premature senescence. Hence, LEMD2 is a new player inthe disease group of laminopathies.
Poor prognostic implications of myelodysplasia-related mutations in both older and younger patients with de novo AML
Authors: Xavier Cheng-Hong Tsai, Kuo-Jui Sun, Min-Yen Lo, Feng-Ming Tien, Yuan-Yeh Kuo, Mei-Hsuan Tseng, Yen-Ling Peng, Yi-Kuang Chuang, Bor-Sheng Ko, Jih-Luh Tang, Hsun-I Sun, Ming-Chih Liu, Chia-Wen Liu, Chien-Chin Lin, Ming Yao, Wen-Chien Chou, Hsin-An Hou, Hwei-Fang Tien
Journal: Blood Cancer Journal (2023)

Abstract A set of myelodysplasia-related (MDS-R) gene mutations are incorporated into the 2022 European LeukemiaNet risk classification as adverse genetic factors for acute myeloid leukemia (AML) based on their poor prognostic impact on older patients. The impact of these mutations on younger patients (age &lt; 60 years) remains elusive. In the study of 1213 patients with de novo non-M3 AML, we identified MDS-R mutations in 32.7% of the total cohort, 44.9% of older patients and 23.4% of younger patients. The patients with MDS-R mutations had a significantly lower complete remission rate in both younger and older age groups. With a median follow-up of 9.2 years, the MDS-R group experienced shorter overall survival ( P = 0.034 for older and 0.035 for younger patients) and event-free survival ( P = 0.004 for older and 0.042 for younger patients). Furthermore, patients with MDS-R mutations more frequently harbored measurable residual disease that was detectable using next generation sequencing at morphological CR than those without MDS-R mutations. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) might ameliorate the negative impact of MDS-R mutations. In summary, AML patients with MDS-R mutations have significantly poorer outcomes regardless of age. More intensive treatment, such as allo-HSCT and/or novel therapies, is warranted for AML patients with MDS-R mutations.
The international consensus classification of myeloid neoplasms and acute leukemias: Myeloproliferative neoplasms
Authors: Jürgen Thiele, Hans Michael Kvasnicka, Attilio Orazi, Umberto Gianelli, Naseema Gangat, Alessandrom M. Vannucchi, Tiziano Barbui, Daniel A. Arber, Ayalew Tefferi
Journal: American Journal of Hematology (2023)
Frontline combination of ponatinib and <scp>hyper‐CVAD</scp> in Philadelphia chromosome‐positive acute lymphoblastic leukemia: 80‐months follow‐up results
Authors: Hagop Kantarjian, Nicholas J. Short, Nitin Jain, Koji Sasaki, Xuelin Huang, Fadi G. Haddad, Issa Khouri, Courtney D. DiNardo, Naveen Pemmaraju, William Wierda, Guillermo Garcia‐Manero, Partow Kebriaei, Rebecca Garris, Sanam Loghavi, Jeffrey Jorgensen, Monica Kwari, Susan O'Brien, Farhad Ravandi, Elias Jabbour
Journal: American Journal of Hematology (2023)

Abstract The combination of ponatinib, a third‐generation BCR::ABL1 tyrosine kinase inhibitor, with hyper‐CVAD chemotherapy resulted in high rates of complete molecular remissions and survival, without the need for stem cell transplantation (SCT) in most patients with Philadelphia chromosome(Ph)‐positive acute lymphocytic leukemia (ALL). Confirming these results in a large cohort of patients with longer follow‐up would establish this regimen as a new standard of care. Adults with newly diagnosed Ph‐positive ALL were treated with the hyper‐CVAD regimen. Ponatinib was added as 45 mg daily × 14 during induction, then 45 mg daily continuously (first 37 patients) or 30 mg daily continuously, with dose reduction to 15 mg daily upon achievement of a complete molecular response (CMR; absence of a detectable BCR::ABL1 transcript by quantitative reverse transcription polymerase‐chain reaction at a sensitivity of 0.01%). Maintenance therapy consisted of daily ponatinib and vincristine‐prednisone monthly for 2 years, followed by daily ponatinib indefinitely. Twelve intrathecal injections of cytarabine alternating with methotrexate were given as central nervous system prophylaxis. The trial is registered on clinicaltrials.gov with the identifier NCT01424982. Eighty‐six patients were treated. Their median age was 46 years (range, 21–80). All 68 patients with active disease at the initiation of therapy achieved complete response (CR) The cumulative CMR rate was 86%. Twenty‐ patients (23%) underwent allogeneic SCT. With a median follow‐up of 80 months (range, 16–129 months), the estimated 6‐year event‐free survival rate was 65% and the overall survival rate was 75%. There was no difference in outcome by performance of allogeneic SCT in first CR. Common grade 3–5 adverse events included infection ( n = 80, 93%), increased liver transaminases ( n = 26, 31%) and total bilirubin ( n = 13, 15%), hypertension ( n = 15, 17%), pancreatitis ( n = 13, 15%), hemorrhage ( n = 12, 13%), and skin rash ( n = 9, 10%). Two ponatinib‐related deaths from myocardial infarction (3%; at months 2.6 and 4.3, respectively; both in CR) in the first 37 patients treated led to the ponatinib dose‐modifications mentioned earlier, with no further ponatinib‐related deaths observed. The long‐term results of ponatinib and hyper‐CVAD continue to demonstrate excellent outcome results and acceptable safety data, indicating that this strategy is another standard of care approach in frontline Ph‐positive ALL.
Сondylar Hyperplasia. Modern Approaches to Diagnostics on the Example of a Clinical Case
Authors: S. N. Prokhorov, N. V. Kochergina, A. D. Ryzhkov, A. S. Krylov, G. M. Karachunskiy, A. B. Bludov
Journal: Radiology - Practice (2022)

The purpose of the work was to demonstrate of the possibilities of SPECT/CT in the diagnosis of condylar hyperplasia in a 17-year-old patient. According to the results of bone scan and SPECT/CT, anatomical and metabolic abnormalities were found, confirming the clinical diagnosis. The use of modern diagnostic methods, in particular SPECT/CT, is justified and recommended for suspected condylar hyperplasia.
Racial and Ethnic Differences in COVID-19 Vaccination Coverage Among Children and Adolescents Aged 5–17 Years and Parental Intent to Vaccinate Their Children — National Immunization Survey–Child COVID Module, United States, December 2020–September 2022
Authors: Madeleine R. Valier, Laurie D. Elam-Evans, Yi Mu, Tammy A. Santibanez, David Yankey, Tianyi Zhou, Cassandra Pingali, James A. Singleton
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

Some racial and ethnic groups are at increased risk for COVID-19 and associated hospitalization and death because of systemic and structural inequities contributing to higher prevalences of high-risk conditions and increased exposure (1). Vaccination is the most effective prevention intervention against COVID-19-related morbidity and mortality*; ensuring more equitable vaccine access is a public health priority. Differences in adult COVID-19 vaccination coverage by race and ethnicity have been previously reported (2,3), but similar information for children and adolescents is limited (4,5). CDC analyzed data from the National Immunization Survey-Child COVID Module (NIS-CCM) to describe racial and ethnic differences in vaccination status, parental intent to vaccinate their child, and behavioral and social drivers of vaccination among children and adolescents aged 5-17 years. By August 31, 2022, approximately one third (33.2%) of children aged 5-11 years, more than one half (59.0%) of children and adolescents aged 12-15 years, and more than two thirds (68.6%) of adolescents aged 16-17 years had received ≥1 COVID-19 vaccine dose. Vaccination coverage was highest among non-Hispanic Asian (Asian) children and adolescents, ranging from 63.4% among those aged 5-11 years to 91.8% among those aged 16-17 years. Coverage was next highest among Hispanic or Latino (Hispanic) children and adolescents (34.5%-77.3%). Coverage was similar for non-Hispanic Black or African American (Black), non-Hispanic White (White), and non-Hispanic other race† or multiple race (other/multiple race) children and adolescents aged 12-15 and 16-17 years. Among children aged 5-11 years, coverage among Black children was lower than that among Hispanic, Asian, and other/multiple race children. Enhanced public health efforts are needed to increase COVID-19 vaccination coverage for all children and adolescents. To address disparities in child and adolescent COVID-19 vaccination coverage, vaccination providers and trusted messengers should provide culturally relevant information and vaccine recommendations and build a higher level of trust among those groups with lower coverage.
Mpox Cases Among Cisgender Women and Pregnant Persons — United States, May 11–November 7, 2022
Authors: Lisa P. Oakley, Kaitlin Hufstetler, Jesse O’Shea, J. Danielle Sharpe, Cristin McArdle, Varsha Neelam, Nicole M. Roth, Emily O. Olsen, Maren Wolf, Leah Zilversmit Pao, Jeremy A. W. Gold, K. Meryl Davis, Dana Perella, Shara Epstein, Maura K. Lash, Olivia Samson, Jessica Pavlick, Amanda Feldpausch, Jennifer Wallace, Atmaram Nambiar, Van Ngo, Umme-Aiman Halai, Claudia W. Richardson, Traci Fowler, Burnestine P. Taylor, Joyce Chou, Lindsey Brandon, Rose Devasia, Erin K. Ricketts, Catherine Stockdale, Mellisa Roskosky, Rachel Ostadkar, Yeng Vang, Romeo R. Galang, Kiran Perkins, Melanie Taylor, Mary Joung Choi, Paul J. Weidle, Patrick Dawson, Sascha Ellington, Cori Dennison, Ian Hennessee, Aspen Riser, LaTweika Salmon-Trejo, Gail Scogin, Emily Sims, Penelope Strid, Raquel Velazquez-Kronen, Claire Xu, Carla Zelaya
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

Monkeypox (mpox) cases in the 2022 outbreak have primarily occurred among adult gay, bisexual, and other men who have sex with men (MSM); however, other populations have also been affected (1). To date, data on mpox in cisgender women and pregnant persons have been limited. Understanding transmission in these populations is critical for mpox prevention. In addition, among pregnant persons, Monkeypox virus can be transmitted to the fetus during pregnancy or to the neonate through close contact during or after birth (2-5). Adverse pregnancy outcomes, including spontaneous abortion and stillbirth, have been reported in previous mpox outbreaks (3). During May 11-November 7, 2022, CDC and U.S. jurisdictional health departments identified mpox in 769 cisgender women aged ≥15 years, representing 2.7% of all reported mpox cases.† Among cases with available data, 44% occurred in cisgender women who were non-Hispanic Black or African American (Black), 25% who were non-Hispanic White (White), and 23% who were Hispanic or Latino (Hispanic). Among cisgender women with available data, 73% reported sexual activity or close intimate contact as the likely route of exposure, with mpox lesions most frequently reported on the legs, arms, and genitals. Twenty-three mpox cases were reported in persons who were pregnant or recently pregnant§; all identified as cisgender women based on the mpox case report form.¶ Four pregnant persons required hospitalization for mpox. Eleven pregnant persons received tecovirimat, and no adverse reactions were reported. Continued studies on mpox transmission risks in populations less commonly affected during the outbreak, including cisgender women and pregnant persons, are important to assess and understand the impact of mpox on sexual, reproductive, and overall health.
First FDA-Approved Gene Therapy for Hemophilia
Authors: Howard Larkin
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Gout Flare and Cardiovascular Events—Reply
Authors: Edoardo Cipolletta, Laila J. Tata, Abhishek Abhishek
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Vascular calcification: Molecular mechanisms and therapeutic interventions
Authors: Wei Pan, Wei Jie, Hui Huang
Journal: MedComm (2023)

Abstract Vascular calcification (VC) is recognized as a pathological vascular disorder associated with various diseases, such as atherosclerosis, hypertension, aortic valve stenosis, coronary artery disease, diabetes mellitus, as well as chronic kidney disease. Therefore, it is a life‐threatening state for human health. There were several studies targeting mechanisms of VC that revealed the importance of vascular smooth muscle cells transdifferentiating, phosphorous and calcium milieu, as well as matrix vesicles on the progress of VC. However, the underlying molecular mechanisms of VC need to be elucidated. Though there is no acknowledged effective therapeutic strategy to reverse or cure VC clinically, recent evidence has proved that VC is not a passive irreversible comorbidity but an active process regulated by many factors. Some available approaches targeting the underlying molecular mechanism provide promising prospects for the therapy of VC. This review aims to summarize the novel findings on molecular mechanisms and therapeutic interventions of VC, including the role of inflammatory responses, endoplasmic reticulum stress, mitochondrial dysfunction, iron homeostasis, metabolic imbalance, and some related signaling pathways on VC progression. We also conclude some recent studies on controversial interventions in the clinical practice of VC, such as calcium channel blockers, renin–angiotensin system inhibitions, statins, bisphosphonates, denosumab, vitamins, and ion conditioning agents.
Present Status of “Insulin”
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Gout Flare and Cardiovascular Events
Authors: Ana Catarina Fonseca
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
High- vs Low-Dose Tranexamic Acid Infusion and Need for Red Blood Cell Transfusion and Adverse Events in Cardiac Surgery
Authors: Andreas Koster, Nikolai Hulde, Armin Zittermann
Journal: JAMA (2023)

To the Editor A recent study1 demonstrated a modest but statistically significant reduction in the number of patients needing red blood cell transfusion with use of high-dose vs low-dose tranexamic acid.
Opportunities for Clinicians and Health Systems to Address Disparities in US Drug Overdose Deaths by Race and Ethnicity
Authors: Margaret Kirkegaard, Bren Manaugh
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Mindfulness Noninferior to Medication for Quelling Anxiety
Authors: Anita Slomski
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal